The proposed study examines the impact and cost associated with an innovative intervention to increase adherence to HIV treatment for HIV-infected (HIV+) adolescents (hereafter Suubi+Adherence). Suubi+Adherence is informed by an efficacious economic empowerment intervention previously tested with AIDS-orphaned children, Suubi-Uganda, and draws from Asset-Theory and previous adherence studies. Suubi+Adherence aims to: 1) promote income-generating activities -- also known as microenterprises -- for poor HIV+ adolescents and their families so that there is sufficient income to meet the specific financial needs associated with managing HIV as a chronic illness and; 2) provide support for adherence to antiretroviral therapy (ART). Studies from Uganda, and much of sub-Saharan Africa (SSA) indicate that one group disproportionately affected by HIV is economically vulnerable children. For this population, adherence to treatment regimens may require a level of economic stability that many youth do not experience. Indeed, the commonly cited reasons for non-adherence are economic in nature, such as lack of resources for medication, transportation to attend clinic appointments, and food and nutritional supplements. Poor children are less likely to adhere to ART and other health-related regimens. Yet, to date, no adherence interventions have focused on the underlying economic drivers, which might help explain why results of adherence interventions with HIV+ adolescents in poverty have had small to moderate effects at best. The proposed study will randomly assign 736 HIV+ adolescents (ages 12 to 15 years at study entry) under the care of 32 health clinics in Rakai, Masaka, and Lwengo Districts of southern Uganda - districts heavily affected by HIV/AIDS - to one of two study conditions: Suubi+Adherence vs. bolstered standard of care (SOC). Assessments will be conducted at baseline, and 12, 24, 36, and 48-months post-intervention initiation. More specifically, we will: 1) examine the impact of the Suubi+Adherence intervention on key adherence to HIV treatment regimen outcomes for HIV+ adolescents, including: participants' ability to access and refill prescribed medication and keep to prescribed daily medication routines: a) not skipping doses, b) taking doses at the right times, c) participants' health literay and health behaviors (e.g. keeping medical appointments, following nutritional recommendations), d) CD4, and HIV-related biomarkers (CD4 T-cell count and viral load); 2) explore the impact of the Suubi+Adherence intervention on potential mechanisms of protective health behaviors, knowledge, and beliefs (e.g. financial stability, sexual risk-taking behavior, personal beliefs about medication, hopelessness, future plans and aspirations, self-efficacy); and 3) examine the costs associated with the Suubi+Adherence. The study will advance knowledge and inform the development of programs aimed at increasing adherence to HIV treatment for HIV+ adolescents in low-resource regions such as SSA. The study will provide crucial evidence about the effects of an economic empowerment program on short, and long-term impacts. PUBLIC HEALTH RELEVANCE: The proposed study represents the first evaluation of the impact and cost associated with an innovative theoretically-guided intervention to increase adherence to HIV treatment for HIV- infected adolescents. The study applies a savings-led microenterprises program for poor HIV+ adolescents so that there is sufficient income to meet the specific needs associated with managing HIV as a chronic illness.